Your browser doesn't support javascript.
Inhibition of SARS-CoV-2 replication by zinc gluconate in combination with hinokitiol.
Tao, Xuan; Zhang, Lu; Du, Liubing; Lu, Kai; Zhao, Zhennan; Xie, Yanxuan; Li, Xiaobo; Huang, Shuxiang; Wang, Pei-Hui; Pan, Ji-An; Xia, Wei; Dai, Jun; Mao, Zong-Wan.
  • Tao X; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China.
  • Zhang L; Guangzhou Customs District Technology Center, No. 66 Huacheng Avenue, Tianhe district, Guangzhou 510700, China.
  • Du L; The Center for Infection and Immunity Study, School of Medicine, Sun Yat-sen University, Guangming Science City, Shenzhen 518107, China.
  • Lu K; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China.
  • Zhao Z; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China.
  • Xie Y; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China.
  • Li X; Guangzhou Customs District Technology Center, No. 66 Huacheng Avenue, Tianhe district, Guangzhou 510700, China.
  • Huang S; Guangzhou Customs District Technology Center, No. 66 Huacheng Avenue, Tianhe district, Guangzhou 510700, China.
  • Wang PH; Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
  • Pan JA; The Center for Infection and Immunity Study, School of Medicine, Sun Yat-sen University, Guangming Science City, Shenzhen 518107, China.
  • Xia W; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address: xiawei5@mail.sysu.edu.cn.
  • Dai J; Guangzhou Customs District Technology Center, No. 66 Huacheng Avenue, Tianhe district, Guangzhou 510700, China.
  • Mao ZW; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address: cesmzw@mail.sysu.edu.cn.
J Inorg Biochem ; 231: 111777, 2022 06.
Article in English | MEDLINE | ID: covidwho-1873158
ABSTRACT
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is currently the major challenge to global public health. Two proteases, papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro or Mpro), are indispensable for SARS-CoV-2 replication, making them attractive targets for antiviral therapy development. Here we screened a panel of essential metal ions using a proteolytic assay and identified that zinc gluconate, a widely-used zinc supplement, strongly inhibited the proteolytic activities of the two proteases in vitro. Biochemical and crystallographic data reveal that zinc gluconate exhibited the inhibitory function via binding to the protease catalytic site residues. We further show that treatment of zinc gluconate in combination with a small molecule ionophore hinokitiol, could lead to elevated intracellular Zn2+ level and thereby significantly impaired the two protease activities in cellulo. Particularly, this approach could also be applied to rescue SARS-CoV-2 infected mammalian cells, indicative of potential application to combat coronavirus infections. Our studies provide the direct experimental evidence that elevated intracellular zinc concentration directly inhibits SARS-CoV-2 replication and suggest the potential benefits to use the zinc supplements for coronavirus disease 2019 (COVID-19) treatment.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals Language: English Journal: J Inorg Biochem Year: 2022 Document Type: Article Affiliation country: J.jinorgbio.2022.111777

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals Language: English Journal: J Inorg Biochem Year: 2022 Document Type: Article Affiliation country: J.jinorgbio.2022.111777